TY - JOUR TI - Ventral hippocampal projections to the medial prefrontal cortex regulate social memory AU - Phillips, Mary L AU - Robinson, Holly Anne AU - Pozzo-Miller, Lucas A2 - Colgin, Laura L A2 - Monteggia, Lisa M A2 - Neul, Jeffrey L VL - 8 PY - 2019 DA - 2019/05/21 SP - e44182 C1 - eLife 2019;8:e44182 DO - 10.7554/eLife.44182 UR - https://doi.org/10.7554/eLife.44182 AB - Inputs from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) are implicated in several neuropsychiatric disorders. Here, we show that the vHIP-mPFC projection is hyperactive in the Mecp2 knockout mouse model of the autism spectrum disorder Rett syndrome, which has deficits in social memory. Long-term excitation of mPFC-projecting vHIP neurons in wild-type mice impaired social memory, whereas their long-term inhibition in Rett mice rescued social memory deficits. The extent of social memory improvement was negatively correlated with vHIP-evoked responses in mPFC slices, on a mouse-per-mouse basis. Acute manipulations of the vHIP-mPFC projection affected social memory in a region and behavior selective manner, suggesting that proper vHIP-mPFC signaling is necessary to recall social memories. In addition, we identified an altered pattern of vHIP innervation of mPFC neurons, and increased synaptic strength of vHIP inputs onto layer five pyramidal neurons as contributing factors of aberrant vHIP-mPFC signaling in Rett mice. KW - social memory KW - ventral hippocampus KW - medial prefrontal cortex KW - Mecp2 KW - Rett syndrome KW - autism JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -